With the rollout of antiretroviral therapy in South Africa and its potential to prolong the lives of HIV-infected individuals, understanding the sexual behavior of HIV-positive people is essential to curbing secondary HIV transmission.
We surveyed 3819 HIV-positive patients during their first visit to an urban wellness clinic and a rural wellness clinic.
Urban residents were more likely than rural residents to have current regular sex partners (75.1% vs. 46.0%; χ2 odds ratio [OR] = 3.531; P < 0.001), to have any current sexual partners (75.3% vs. 51.2%; χ2 OR = 2.908; P < 0.001), and to report consistent condom use with regular partners (78.4% vs. 48.3%; χ2 OR = 3.886; P < 0.001) and with casual partners (68.6% vs. 48.3%; χ2 OR = 2.337; P < 0.001). In multivariate analysis, independent predictors of consistent condom use with regular partners included across gender, urban residence, and higher education levels; for women, disclosure and younger age; and for men only, no history of alcohol consumption. Male and female participants with a casual sexual partner were less likely to use a condom consistently with regular partners. Additionally, urban residence and a CD4 count greater than 200 cells/mm3 as well as (for women only) a higher household income and a history of alcohol consumption were predictors of having a regular sexual partner.
HIV prevention programs in South Africa that emphasize the importance of condom use and disclosure and are tailored to the needs of their attending populations are critical given the potential for HIV-infected individuals to resume risky sexual behavior with improving health.
condom use; HIV prevention; positive prevention; sexual behavior; South Africa; urban-rural
We assessed prevalence and factors associated with hepatitis B in a cross-section of HIV-infected primary care and anti-natal clinic patients in South Africa and evaluated a rapid hepatitis B surface antigen (HBsAg) assay. We enrolled 998 patients; 88% were women, median age was 29 years, and median CD4 count was 354 cells/mm3. HBsAg ELISA, anti-hepatitis B core (HBc) antibodies, and hepatitis C virus antibody were positive among 4.2%, 37%, and 0.1% of subjects, respectively. Univariate and multivariate associations were assessed using logistic regression. Anti-HBc antibodies were associated with alcohol use, traditional medicines, and higher CD4. HBsAg positivity was associated with lower CD4. Compared to the HBsAg ELISA, a rapid HBsAg test had a sensitivity of 75.0% and specificity of 99.6%. In conclusion, we identified a moderate prevalence of both HBsAg and anti-HBc. Importantly, we found subjects with HBsAg positivity had lower CD4 counts.
HIV/AIDS; HBV; HBsAg; HCV; rapid test; Africa
To determine the impact of HAART on incidence, regression, and progression of cytopathological abnormalities in HIV-infected women.
HIV-infected women (N=1123) from Soweto, South Africa underwent serial cervical smears that were analyzed and reported using the Bethesda System. The results of HAART and non-HAART users were compared using two statistical approaches: a survival analysis assessing risk of incident smear abnormality among women with baseline normal smear results; and analysis with marginal models assessing for an association between HAART use and likelihood of regression/progression in consecutive smears.
After multivariate survival analysis, women using HAART with a normal baseline smear were 38% less likely to have an incident smear abnormality during follow-up than nonusers [confidence interval (CI) 0.42–0.91; P=0.01]. Multivariate marginal models analysis identified a significantly increased likelihood (odds ratio 2.61; CI 1.75–3.89; P< 0.0001) of regression of cervical lesions among women on HAART.
Our large prospective cohort study adds significant weight to the side of the balance of clinical research supporting the positive impact of HAART on the natural history of human papillomavirus-related cervical disease in HIV-infected women.
cervical cancer; disease progression; disease regression; HAART; Papanicolaou smear
Symptom screening is a recommended component of intensified case-finding (ICF) for pulmonary tuberculosis (TB) among HIV-infected individuals. Symptomatic individuals are further investigated to either exclude or diagnose pulmonary TB, thus reducing the number of individuals requiring costly laboratory investigation. Those with laboratory evaluations negative for pulmonary TB or who lack symptoms may be eligible for antiretroviral therapy (ART) and/or TB isoniazid preventive therapy (IPT). A four-part symptom screen has been recommended by the World Health Organization (WHO) for identifying TB suspects and those unlikely to have TB. A meta-analysis of studies among HIV-infected individuals calculated a sensitivity of 90.1% for the four-part symptoms screen - of any of cough, fever, night sweats, or weight loss - among patients in clinical care, making it an effective tool for identifying most patients with TB. An important population for intensified case-finding not included in that meta-analysis was HIV-infected pregnant women. We undertook a cross-sectional survey among HIV-infected pregnant women receiving prenatal care at community clinics in South Africa. We obtained a four-symptom review and sputum smear microscopy and mycobacterial culture on all participants. Among 1415 women, 226 (16%) had a positive symptom screen, and 35 (2.5%) were newly diagnosed with culture-positive TB. Twelve were on TB treatment at the time of screening, yielding 47 (3.3%) women with prevalent TB. Symptom screening among women without known TB had a sensitivity of 28% and specificity of 84%. The poor performance of symptom screening to identify women with TB suggests that other approaches may be needed for intensified case-finding to be effective for this population.
We studied 1163 sexually-active HIV-infected South African men and women in an urban primary care program to understand patterns of sexual behaviors and whether these behaviors differed by partner HIV status. Overall, 40% reported a HIV-positive partner and 60% a HIV-negative or status unknown partner; and 17.5% reported >2 sex acts in the last 2 weeks, 16.4% unprotected sex in the last 6 months, and 3.7% >1 sex partner in the last 6 months. Antiretroviral therapy (ART) was consistently associated with decreased sexual risk behaviors, as well as with reporting a HIV-negative or status unknown partner. The odds of sexual risk behaviors differed by sex; and were generally higher among participants reporting a HIV-positive partner, but continued among those with a HIV-negative or status unknown partner. These data support ART as a means of HIV prevention. Engaging in sexual risk behaviors primarily with HIV-positive partners was not widely practiced in this setting, emphasizing the need for couples-based prevention.
HIV; AIDS; South Africa; Sexual risk behavior; ART
Mortality in the first months of antiretroviral therapy (ART) is a significant clinical problem in sub-Saharan Africa. To date, no post-mortem study has investigated the causes of mortality in these patients.
HIV-positive adults who died as in-patients at a Johannesburg academic hospital underwent chart-review and ultrasound-guided needle autopsy for histological and microbiological examination of lung, liver, spleen, kidney, bone marrow, lymph node, skin and cerebrospinal fluid. A clinico-pathologic committee considered all available data and adjudicated immediate and contributing causes of death.
Thirty-nine adults were enrolled: 14 pre-ART, 15 early-ART (7–90 days), and 10 late-ART (>90 days). Needle sampling yielded adequate specimen in 100% of kidney, skin, heart and cerebrospinal fluid samples, 97% of livers and lungs, 92% of bone marrows, 87% of spleens and 68% of lymph nodes. Mycobacterial infections were implicated in 69% of deaths (26 of 27 of these due to M. tuberculosis), bacterial infections in 33%, fungal infections in 21%, neoplasm in 26%, and non-infectious organ failure in 26%. Immune reconstitution inflammatory syndrome (IRIS) was implicated in 73% of early-ART deaths. Post-mortem investigations revealed previously undiagnosed causes of death in 49% of cases. Multiple pathologies were common with 62% of subjects with mycobacterial infection also having at least one other infectious or neoplastic cause of death.
Needle biopsy was efficient and yielded excellent pathology. The large majority of deaths in all three groups were caused by M. tuberculosis suggesting an urgent need for improved diagnosis and expedited treatment prior to and throughout the course of antiretroviral therapy. Complex, unrecognized co-morbidities pose an additional challenge.
Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) share transmission routes and are endemic in sub-Saharan Africa. The objective of the present study was to use the Taormina definition of occult HBV infection, together with stringent amplification conditions, to determine the prevalence and characteristics of HBV infection in antiretroviral treatment (ART)-naïve HIV+ve adults in a rural cohort in South Africa. The presence of HBV serological markers was determined by enzyme linked immunoassay (ELISA) tests. HBV DNA-positivity was determined by polymerase chain reaction (PCR) of at least two of three different regions of the HBV genome. HBV viral loads were determined by real-time PCR. Liver fibrosis was determined using the aspartate aminotransferase-to-platelet ratio index. Of the 298 participants, 231 (77.5%) showed at least one HBV marker, with 53.7% HBV DNA−ve (resolved) and 23.8% HBV DNA+ve (current) [8.7% HBsAg+ve: 15.1% HBsAg−ve]. Only the total number of sexual partners distinguished HBV DNA+ve and HBV DNA−ve participants, implicating sexual transmission of HBV and/or HIV. It is plausible that sexual transmission of HBV and/or HIV may result in a new HBV infection, superinfection and re-activation as a consequence of immunesuppression. Three HBsAg−ve HBV DNA+ve participants had HBV viral loads <200 IU/ml and were therefore true occult HBV infections. The majority of HBsAg−ve HBV DNA+ve participants did not differ from HBsAg+ve HBV DNA+ve (overt) participants in terms of HBV viral loads, ALT levels or frequency of liver fibrosis. Close to a quarter of HIV+ve participants were HBV DNA+ve, of which the majority were HBsAg−ve and were only detected using nucleic acid testing. Detection of HBsAg−ve HBV DNA+ve subjects is advisable considering they were clinically indistinguishable from HBsAg+ve HBV DNA+ve individuals and should not be overlooked, especially if lamivudine is included in the ART.
Human immunodeficiency virus (HIV) and tuberculosis (TB) are among the leading causes of death among women of reproductive age worldwide. TB is a significant cause of maternal morbidity. Detection of TB during pregnancy could provide substantial benefits to women and their offspring.
This was a cross-sectional implementation research study of integrating active TB case-finding with delivery of antenatal and prevention of mother-to-child transmission (PMTCT) services in six clinics in Soweto, South Africa. All pregnant women ≥18 years of age presenting for routine care to these public clinics were screened for symptoms of active TB, cough ≥2 weeks, sputum production, fevers, night sweats or weight loss, regardless of their HIV status. Participants with any symptom of active TB were asked to provide a sputum specimen for smear microscopy, mycobacterial culture and drug-susceptibility testing.
Between December 2008 and July 2009, 3,963 pregnant women were enrolled and screened for TB, of whom 1,454 (36.7%) were HIV-seropositive. Any symptom of TB was reported by 23.1% of HIV-seropositive and 13.8% of HIV-seronegative women (p<0.01). Active pulmonary TB was diagnosed in 10/1,454 HIV-seropositve women (688 per 100,000) and 5/2,483 HIV-seronegative women (201 per 100,000, p = 0.03). The median CD4+ T-cell count among HIV-seropositive women with TB was similar to that of HIV-seropositive women without TB (352 versus 333 cells/μL, p=0.85).
There is a high burden of active TB among HIV-seropositive pregnant women. TB screening and provision of isoniazid preventive therapy and antiretroviral therapy should be integrated with PMTCT services.
tuberculosis; HIV; pregnancy; epidemiology; screening
Treatment of latent tuberculosis in patients infected with the human immunodeficiency virus (HIV) is efficacious, but few patients around the world receive such treatment. We evaluated three new regimens for latent tuberculosis that may be more potent and durable than standard isoniazid treatment.
We randomly assigned South African adults with HIV infection and a positive tuberculin skin test who were not taking antiretroviral therapy to receive rifapentine (900 mg) plus isoniazid (900 mg) weekly for 12 weeks, rifampin (600 mg) plus isoniazid (900 mg) twice weekly for 12 weeks, isoniazid (300 mg) daily for up to 6 years (continuous isoniazid), or isoniazid (300 mg) daily for 6 months (control group). The primary end point was tuberculosis-free survival.
The 1148 patients had a median age of 30 years and a median CD4 cell count of 484 per cubic millimeter. Incidence rates of active tuberculosis or death were 3.1 per 100 person-years in the rifapentine–isoniazid group, 2.9 per 100 person-years in the rifampin–isoniazid group, and 2.7 per 100 person-years in the continuous-isoniazid group, as compared with 3.6 per 100 person-years in the control group (P>0.05 for all comparisons). Serious adverse reactions were more common in the continuous-isoniazid group (18.4 per 100 person-years) than in the other treatment groups (8.7 to 15.4 per 100 person-years). Two of 58 isolates of Mycobacterium tuberculosis (3.4%) were found to have multidrug resistance.
On the basis of the expected rates of tuberculosis in this population of HIV-infected adults, all secondary prophylactic regimens were effective. Neither a 3-month course of intermittent rifapentine or rifampin with isoniazid nor continuous isoniazid was superior to 6 months of isoniazid.
To study significant predictors of condom use in HIV-infected adults, we propose the use of generalized partially linear models and develop a variable selection procedure incorporating a least squares approximation. Local polynomial regression and spline smoothing techniques are used to estimate the baseline nonparametric function. The asymptotic normality of the resulting estimate is established. We further demonstrate that, with the proper choice of the penalty functions and the regularization parameter, the resulting estimate performs as well as an oracle procedure. Finite sample performance of the proposed inference procedure is assessed by Monte Carlo simulation studies. An application to assess condom use by HIV-infected patients gains some interesting results, which can not be obtained when an ordinary logistic model is used.
AIDS; Condom use; LASSO; Least squares approximation; Local linear regression; Profile likelihood; Quasilikelihood; SCAD; Sexual behavior; Spline smoothing
Although tuberculosis (TB) continues to cause enormous suffering and overwhelm health care systems in areas with high HIV prevalence, there have been a number of recent significant advances in knowledge regarding the epidemiology, management, and control of HIV-related TB. TB remains the most common serious opportunistic infection in people with HIV infection and the leading cause of death. However, there is some reason for optimism. First, two trials addressing when to start antiretroviral therapy (ART) in HIV-infected adults with newly diagnosed TB have shown that earlier initiation of ART reduces mortality significantly. Second, there is trial evidence of efficacy in giving long-term isoniazid preventive treatment (IPT) to HIV-infected adults in high HIV–prevalence settings where TB reinfection is frequent (much like cotrimoxazole). Third, the search for an inexpensive, rapid, sensitive, and specific TB diagnostic that is able to replace smear and delayed mycobacterial culture has yielded promising results. Responding to massive TB epidemics in high HIV–prevalence settings, the World Health Organization has supplemented its directly observed treatment short-course strategy with one called the 3I's to actively screen and diagnose TB cases (intensified case finding), prevent new cases of TB with IPT, and prevent transmission of TB in congregate settings such as hospitals and clinics (infection control). Combating TB in high HIV–prevalence settings requires rapid and massive implementation of the 3I's with initiation of antiretrovirals and more effective efforts to prevent new HIV infections.
preventive treatment; antiretroviral therapy; Xpert MTB Rif; intensified case finding
To substantiate reports of greater emergence of the K65R nucleoside reverse transcriptase inhibitor (NRTI) mutation in human immunodeficiency virus type 1 (HIV-1) subtype C, we examined natural low-level K65R expression in subtype C relative to subtypes B and AE. We used allele-specific polymerase chain reaction to screen HIV-1 amplified by reverse-transcription high-fidelity polymerase chain reaction from subtype C–infected South African women and infants and CRF01(subtype AE) from Thailand; all subjects were NRTI naive. We found low-level K65R of unknown clinical significance in NRTI-naive subtype C–infected women and infants at frequencies above the natural occurrence in subtypes B and AE. The frequent appearance of subtype C frameshift deletions at codon 65 supports a propensity for transcription error in this region.
To determine rates and predictors of treatment refusal in newly identified HIV-infected individuals in Soweto, South Africa
We analyzed data from adult clients (> 18 years) presenting for voluntary counseling and testing (VCT) at the Zazi Testing Center, Perinatal HIV Research Unit to determine rates of antiretroviral therapy (ART) refusal among treatment-eligible, HIV-infected individuals (CD4+ <200 cells/mm3 or WHO stage 4). Multiple logistic regression models were used to investigate factors associated with refusal.
From December 2008 to December 2009, 7287 adult clients were HIV tested after counseling. 2562 (35%) were HIV-infected, of whom 743 (29%) were eligible for immediate ART. One-hundred and forty-eight (20%) refused referral to initiate ART, most of whom (92%) continued to refuse after 2 months of counseling. The leading reason for ART refusal was given as “feeling healthy” (37%), despite clients having a median CD4+ cell count of 110 cells/mm3 and triple the rate of active tuberculosis as seen in non-refusers. In adjusted models, single clients (AOR= 1.80, 95% CI: 1.06–3.06) and those with active tuberculosis (AOR = 3.50, 95% CI: 1.55–6.61) were more likely to refuse ART.
Nearly one in five treatment-eligible HIV-infected individuals in Soweto refused to initiate ART after VCT, putting them at higher risk for early mortality. “Feeling healthy” was given as the most common reason to refuse ART, despite a suppressed CD4+ count and co-morbidities, such as tuberculosis. These findings highlight the urgent need for research to inform interventions targeting ART refusers.
africa; HIV; refusal; treatment; VCT
To ascertain progression and regression of cervical dysplasia in HIV-infected women in Soweto.
Women attending an HIV wellness clinic were offered cervical smears as part of care; smears were assessed using the Bethesda system. Those with high grade lesions or worse were referred for colposcopy. Progression analyses included women with at least two smears ≥5.5 months apart. Hazard ratios (HR) were used to ascertain predictors of progression.
2,325 women had a baseline smear; their median age and CD4 count was 32 yrs and 312 cells/μl respectively; 17% were taking highly active antiretroviral therapy (HAART); 62%, 20% and 14% had normal, low grade squamous intraepithelial lesions (LSIL) or high grade squamous intraepithelial lesions (HSIL), respectively. Of those with baseline normal or LSIL smears, 1,074 had another smear; progression from normal to LSIL was 9.6/100py (95% CI 8.3-11.1) and progression from normal or LSIL to HSIL was 4.6/100py (95% CI 3.9-5.5). Of 225 women with LSIL at baseline and ≥1 subsequent smear ≥11.5 months later, 44.0% regressed to normal (21.2/100py (95% CI 17.5-25.7)). Multivariate models suggested risk for progression in women with CD4 count <200; HAART reduced the risk of progression (aHR 0.72 [0.52-0.99]).
HIV-infected women have high rates of prevalent and incident HSIL and LSIL with relatively low risk of regression to normal from LSIL. HAART appears to protect against progression. Our findings suggest cervical screening intervals should be less than 10 years - irrespective of age in women with CD4 counts under 500 cells/mm3.
antiretroviral therapy; cohort; squamous intraepithelial lesion; CD4; cervical cancer; HPV
Although 900,000 HIV-infected South Africans receive antiretroviral therapy (ART), the majority of South Africans with HIV remain undiagnosed.
We use a published simulation model of HIV case detection and treatment to examine three HIV screening scenarios, in addition to current practice: 1) one-time; 2) every five years; and 3) annually. South African model input data include: 16.9% HIV prevalence, 1.3% annual incidence, 49% test acceptance rate, HIV testing costs of $6.49/patient, and a 47% linkage-to-care rate (including two sequential ART regimens) for identified cases. Outcomes include life expectancy, direct medical costs, and incremental cost-effectiveness.
HIV screening one-time, every five years, and annually increase HIV-infected quality-adjusted life expectancy (mean age 33 years) from 180.6 months (current practice) to 184.9, 187.6 and 197.2 months. The incremental cost-effectiveness of one-time screening is dominated by screening every five years. Screening every five years and annually each have incremental cost-effectiveness ratios of $1,570/quality-adjusted life year (QALY) and $1,720/QALY. Screening annually is very cost-effective even in settings with the lowest incidence/prevalence, with test acceptance and linkage rates both as low as 20%, or when accounting for a stigma impact at least four-fold that of the base case.
In South Africa, annual voluntary HIV screening offers substantial clinical benefit and is very cost-effective, even with highly constrained access to care and treatment.
HIV; screening; cost-effectiveness; South Africa
In light of increasing access to highly active antiretroviral treatment (HAART) in sub-Saharan Africa, we conducted a longitudinal study to assess the impact of HAART on sexual risk behaviors among HIV-infected South Africans in urban and rural primary care clinics.
Prospective observational cohort study.
We conducted a cohort study at rural and urban primary care HIV clinics in South Africa consisting of 1544 men and 4719 women enrolled from 2003–2010, representing 19703 clinic visits. The primary outcomes were being sexually active, unprotected sex, and >1 sex partner and were evaluated at six monthly intervals. Generalized estimated equations assessed the impact of HAART on sexual risk behaviors.
Among 6263 HIV-infected men and women, over a third (37.2%) initiated HAART during study follow-up. In comparison to pre-HAART follow-up, visits while receiving HAART were associated with a decrease in those reporting being sexually active (AOR: 0.86 [95% CI: 0.78–0.95]). Unprotected sex and having >1 sex partner were reduced at visits following HAART initiation compared to pre-HAART visits (AOR: 0.40 [95% CI: 0.34–0.46] and AOR: 0.20 [95% CI: 0.14–0.29], respectively).
Sexual risk behavior significantly decreased following HAART initiation among HIV-infected South African men and women in primary care programs. The further expansion of antiretroviral treatment programs could enhance HIV prevention efforts in Africa.
South Africa; HAART; antiretroviral therapy; sexual behavior; HIV transmission; AIDS; HIV
QuantiFERON-TB Gold In Tube (QFT-GIT) is a tool for detecting M. tuberculosis infection. However, interpretation and utility of serial QFT-GIT testing of pediatric tuberculosis (TB) contacts is not well understood. We compared TB prevalence between baseline and 6 months follow-up using QFT-GIT and tuberculin skin testing (TST) in children who were household contacts of adults with pulmonary TB in South Africa, and explored factors associated with QFT-GIT conversions and reversions.
Prospective study with six month longitudinal follow-up.
Among 270 enrolled pediatric contacts, 196 (73%) underwent 6-month follow-up testing. The 6-month prevalence estimate of MTB infection in pediatric contacts increased significantly from a baseline of 29% (79/270, 95%CI [24–35]) to 38% (103/270, 95% CI [32–44], p<0.001) using QFT-GIT; prevalence increased from a baseline of 28% (71/254, 95%CI [23–34]) to 33% (88/263, 95%CI [21–32], p = 0.002) using TST. Prevalence estimates were influenced by thresholds for positivity for TST, but not for QFT-GIT. Among 134 children with a negative or indeterminate baseline QFT-GIT, 24 (18%) converted to positive at follow-up; conversion rates did not differ significantly when using more stringent thresholds to define QFT-GIT conversion. Older age >10 years (AOR 8.9 95%CI [1.1–72]) and baseline TST positivity ≥5 mm (AOR 5.2 95%CI [1.2–23]) were associated with QFT-GIT conversion. Among 62 children with a positive baseline QFT-GIT, 9 (15%) reverted to negative; female gender (AOR 18.5 95%CI [1.1–321]; p = 0.04] was associated with reversion, while children with baseline positive TST were less likely to have QFT-GIT reversion (AOR 0.01 95%CI [0.001–0.24]).
Among pediatric contacts of adult household TB cases in South Africa, prevalence estimates of TB infection increased significantly from baseline to 6 months. Conversions and reversions occurred among pediatric TB contacts using QFT-GIT, but QFT-GIT conversion rates were less influenced by thresholds used for conversions than were TST conversion rates.
Results of international clinical trials assessing when to initiate antiretroviral therapy (ART) will not be available for several years.
To inform HIV treatment decisions over the short- and long-term regarding the optimal CD4 threshold at which to initiate ART in South Africa, while awaiting “when to start” trial results.
Cost-effectiveness analysis using a computer simulation model of HIV disease.
Published data from randomized trials and observational cohorts in South Africa.
HIV-infected patients in South Africa.
Five-year and lifetime.
No treatment, initiate ART at CD4<250/μl, and initiate ART at CD4<350/μl.
Morbidity, mortality, life expectancy, medical costs, and cost-effectiveness.
Results of Base-Case Analysis
If 10-100% of HIV-infected patients are diagnosed and linked to care, initiating ART at CD4<350/μl would reduce severe opportunistic diseases by 22,000-221,000 and deaths by 25,000-253,000 during the next 5 years, compared to initiating ART at CD4<250/μl; cost increases would range from $142 million (10%) to $1.4 billion (100%). Either ART strategy increased long-term survival by at least 7.9 years, with a mean per person life expectancy of 3.8 years for no ART and 12.5 years for ART at <350/μl. Compared to initiating ART at <250/μl, initiating ART at <350/μl had an incremental cost-effectiveness ratio of $1,200/year of life saved.
Results of Sensitivity Analysis
Initiating ART at CD4<350/μl remained cost-effective over the next 5 years even if the probability that the trial would demonstrate superiority to earlier therapy is as low as 17%.
This model does not consider the possible benefits of ART initiation at CD4>350/μl nor reduced HIV transmission.
Earlier ART initiation in South Africa will likely reduce morbidity and mortality, improve long-term survival, and be very cost-effective. While awaiting trial results, treatment guidelines should be liberalized to allow for earlier ART initiation (CD4<350/μl) than is currently recommended.
Resource-limited setting; antiretroviral therapy; ART; cost-effectiveness; HIV
As access to antiretroviral therapy (ART) in sub-Saharan Africa expands, estimates of the costs of initiating and maintaining patients on antiretroviral therapy are important to program planning, budgeting, and cost-effectiveness analyses.
Total costs of providing HIV care, including ART, in an urban, non-governmental, adult clinic in Soweto, South Africa were estimated from October 2004 through March 2005. Personnel costs were estimated using individuals’ work time and salary, and for across-organization services (e.g. information technology), a proportion of entire annual costs was applied. Utilisation of medications, labs, and radiographic tests were estimated by a random sample of patient charts (10%) and applied to the entire cohort.
966 adult patients received care during the study period (75% female, median age 34 years, median CD4 count at ART initiation: 109 cells/mm3). 17% were stable on ART at entry, 61% initiated ART, and 22% did not receive ART over the course of the study. Mean cost of the entire program (in US$) was $92,388/month, and mean per patient cost of care - regardless of ART treatment status - was $98.1/month. Among adults on ART, costs were lowest for those already on ART ($119.0/month) and highest for those initiating ART ($209.7/month) in the first month and $130.0 the following month. Human resources and antiretrovirals each accounted for one-third of overall costs.
The monthly cost of treating HIV-infected patients in an urban South African clinic was highest in the month of initiation and lower for stable patients, with costs driven predominantly by antiretrovirals and personnel.
Costs; antiretroviral therapy; PEPFAR; HIV; South Africa
The World Health Organization recommends isoniazid preventive therapy (IPT) for preventing tuberculosis in HIV-infected adults, although few countries have instituted this policy. Both IPT and highly active antiretroviral therapy (HAART) used separately result in reductions in tuberculosis risk. There is less information on the combined effect of IPT and HAART. We assessed the effect of IPT, HAART or both IPT and HAART on tuberculosis incidence in HIV-infected adults in South Africa.
Two clinical cohorts of HIV-infected patients were studied. Primary exposures were receipt of IPT and/or HAART and the primary outcome was incident tuberculosis. Crude incident rates and incident rate ratios were calculated and Cox proportional hazards models investigated associations with tuberculosis risk.
Among 2778 HIV-infected patients followed for 4287 person-years, 267 incident tuberculosis cases were diagnosed [incidence rate ratio (IRR) = 6.2/100 person-years; 95% CI 5.5–7.0]. For person-time without IPT or HAART, the IRR was 7.1/100 person-years (95% CI 6.2–8.2); for person-time receiving HAART but without IPT, the IRR was 4.6/100 person-years (95% CI 3.4–6.2); for person-time after IPT but prior to HAART, the IRR was 5.2/100 person-years (95% CI 3.4–7.8); during follow-up in patients treated with HAART after receiving IPT the IRR was 1.1/100 person-years (95% CI 0.02–7.6). Compared to treatment-naive patients, HAART-only patients had a 64% decreased hazard for tuberculosis [adjusted hazard ratio (aHR) = 0.36; 95% CI 0.25–0.51], and patients receiving HAART after IPT had a 89% reduced hazard (aHR = 0.11; 95% CI 0.02–0.78).
Tuberculosis risk is significantly reduced by IPT in HAART-treated adults in a high-incidence operational setting in South Africa. IPT is an inexpensive and cost-effective strategy and our data strengthen calls for the implementation of IPT in conjunction with the roll-out of HAART.
HAART; isoniazid; preventive treatment; sub-Saharan Africa; tuberculosis
High BMI has been shown to be protective against tuberculosis (TB) among HIV-uninfected individuals, as well as against disease progression and mortality among those with HIV. We examined the effect of BMI on all-cause mortality and TB incidence among a cohort of HIV-infected adults in Soweto, South Africa.
A clinical cohort of 3456 HIV-infected adults from South Africa was prospectively followed from 2003 to 2008 with regular monitoring. The primary exposure was BMI and the outcomes of interest were all-cause mortality and a newly diagnosed episode of TB. Cox proportional hazard models assessed associations with risk of mortality or incident TB.
Incidence rates of mortality were 10.4/100 person-years for baseline BMI of 18.5 or less, 3.6/100 person-years for baseline BMI 18.6–25, 1.7/100 person-years for baseline BMI 25.1–30, and 1.6/100 person-years for baseline BMI more than 30. Compared to those with normal BMI, overweight and obese participants had a significantly reduced risk of mortality [adjusted hazard ratio 0.59 (95% confidence interval, CI 0.40–0.87) and 0.48 (95% CI 0.29–0.80), respectively]. Incidence rates of TB by baseline BMI were 7.3/100 person-years for underweight, 6.0/100 person-years for normal, 3.2/100 person-years for overweight, and 1.9/100 person-years for obese. Compared to those with normal BMI, those with overweight and obese BMI were at a significantly reduced risk of developing TB [adjusted hazard ratio 0.56 (95% CI 0.38–0.83) and 0.33 (95% CI 0.19–0.55), respectively].
HIV-infected individuals with obese and overweight BMI have a significantly reduced risk of both mortality and TB, after adjusting for HAART use and CD4 cell count.
body mass index; HAART; HIV; mortality; nutrition; tuberculosis
Traditional tuberculosis (TB) treatment outcome measures, such as cure rate, do not provide insight into the underlying reasons for missing clinical targets. We evaluated a TB Process-Based Performance Review (TB-PBPR) tool, developed to identify "missed opportunities" for timely and accurate diagnosis of TB. The tool enables performance assessment at the level of process and quality of care.
The TB-PBPR tool is a single-page structured flow-sheet that identifies 14 clinical actions (grouped into elicited symptoms, clinical examination and investigations). Medical records from selected deceased patients were reviewed at two South African mine hospitals (A = 56 cases; B = 26 cases), a South African teaching hospital (C = 20 cases) and a UK teaching hospital (D = 13 cases).
In hospital A, where autopsy was routine, TB was missed in life in 52% (23/44) of cases and was wrongly attributed as the cause of death in 16% (18/110). Clinical omissions were identified at each hospital and at every stage of clinical management. For example, recording of chest symptoms was omitted in up to 39% of cases, sputum smear examination in up to 85% and chest radiograph in up to 38% of cases respectively.
This study introduces the TB-PBPR tool as a novel method to review and evaluate clinical performance in TB management. We found that simple clinical actions were omitted in many cases. The tool, in conjunction with a manual describing best practice, is adaptable to a range of settings, is educational and enables detailed feedback within a TB programme. The TB-PBPR tool and manual are both freely available for general use.
Urinary lipoarabinomannan (LAM) detection is a promising approach for rapid diagnosis of active tuberculosis (TB). In microbiologically confirmed TB patients, quantitative LAM detection results increased progressively with bacillary burden and immunosuppression. Patients with disseminated TB and/or advanced HIV are target populations for whom urine LAM detection may be particularly useful.
Effective tuberculosis (TB) control in HIV-prevalent settings is hindered by absence of accurate, rapid TB diagnostic tests. We evaluated the accuracy of a urine lipoarabinomannan (LAM) test for TB diagnosis in South Africa.
Hospitalized adults with signs and/or symptoms of active TB were enrolled. Sputum smear microscopy and mycobacterial culture, mycobacterial blood culture, and HIV testing were performed. A spot urine specimen was tested for LAM.
499 participants were enrolled; 422 (84.6%) were HIV-infected. In microbiologically-confirmed TB patients, the LAM test was positive in 114/193 (sensitivity 59%, [95% CI 52, 66]), including 112/167 (67% [59, 74]) who were HIV-infected. Among individuals classified as “not TB”, the LAM test was negative in 117/122 (specificity 96% [91, 99]), including 83/88 (94% [87, 98]) who were HIV-infected. In confirmed TB patients, the LAM test was more sensitive than sputum smear microscopy (42%, 82/193, p<0.001) and detected 56% (62/111) of those who were sputum smear-negative. HIV-infection (AOR 13.4), mycobacteremia (AOR 3.21), and positive sputum smear (AOR 2.42) were risk factors for a positive LAM test.
The urine LAM test detected a subset of HIV-infected patients with severe TB in whom sputum smear microscopy had suboptimal sensitivity. The combination of urine LAM testing and sputum smear microscopy is attractive for use in settings with high HIV burden.
HIV; acquired immunodeficiency syndrome; tuberculosis; mycobacterium infections; diagnosis