[show abstract][hide abstract] ABSTRACT: Little is known about the impact of pregnancy on response to highly active antiretroviral therapy (HAART) in sub-Saharan Africa. We examined the effect of incident pregnancy after HAART initiation on clinical response to HAART.
We evaluated a prospective clinical cohort of adult women initiating HAART in Johannesburg, South Africa between 1 April 2004 and 31 March 2011, and followed up until an event, transfer, drop-out, or administrative end of follow-up on 30 September 2011. Women over age 45 and women who were pregnant at HAART initiation were excluded from the study. Main exposure was having experienced pregnancy after HAART initiation; main outcome was death and (separately) death or new AIDS event. We calculated adjusted hazard ratios (HRs) and 95% confidence limits (CL) using marginal structural Cox proportional hazards models.
The study included 7,534 women, and 20,813 person-years of follow-up; 918 women had at least one recognized pregnancy during follow-up. For death alone, the weighted (adjusted) HR was 0.84 (95% CL 0.44, 1.60). Sensitivity analyses confirmed main results, and results were similar for analysis of death or new AIDS event. Incident pregnancy was associated with a substantially reduced hazard of drop-out (HR = 0.62, 95% CL 0.51, 0.75).
Recognized incident pregnancy after HAART initiation was not associated with increases in hazard of clinical events, but was associated with a decreased hazard of drop-out. High rates of pregnancy after initiation of HAART may point to a need to better integrate family planning services into clinical care for HIV-infected women.
PLoS ONE 01/2013; 8(3):e58117. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: OBJECTIVE:: Recent studies have raised concerns about a change in rates of pregnancy among HIV-negative women exposed to tenofovir.Here, our objective was todetermine among HIV-positive women whether use of tenofovir at HAART initiation or thereafter is associated with subsequent changes in incidence of pregnancy. DESIGN:: Analysis of prospectively collected clinical data. METHODS:: We used Cox proportional hazards models and logistic regression to estimate hazard ratios and odds-ratios for the association of baseline tenofovir use and time to first incident pregnancy. We used marginal structural Cox models to estimate hazard ratios for the association of current tenofovir use and time to first incident pregnancy. RESULTS:: We studied 7,275 women, of whom 1,199 were initiated on tenofovir-based HAART regimens, and who experienced a total of 894 pregnancies in 17,200 person-years of follow-up. Analyses showed slight reductions in hazards of pregnancy among women who used tenofovir, but without sufficient precision to draw strong conclusions. Sensitivity analyses confirmed main results. CONCLUSIONS:: Tenofovir may be associated with a lower hazard or rate of pregnancy in women receiving HAART. However, conclusions are limited by low precision, the observational nature of the data, and possible uncontrolled confounding by temporal trends in contraception use and other factors.
AIDS (London, England) 08/2012; · 4.91 Impact Factor
[show abstract][hide abstract] ABSTRACT: Peripheral neuropathy (PN) is associated with advanced HIV disease and may be a complication of antiretroviral therapy (ART) or anti-tuberculosis (TB) drugs, specifically isoniazid (INH). The effect of non-ART-drug-related PN on treatment outcomes is yet to be determined. We analysed prospectively collected cohort data for HIV-infected ART-naive adults initiating ART at the Themba Lethu Clinic, Johannesburg, South Africa from June 2004 to June 2009. Patients who presented with signs and symptoms of numbness or dysesthesia prior to initiation of ART were defined as having PN. Cox proportional hazard models were used to estimate the effect of PN alone (HIV-related PN) or PN with a history of INH use (TB-related PN) on mortality, lost to follow-up (LTFU), persistent and recurrent PN by 12 months of follow-up. Of the 9,399 patients initiating ART, 3.9 % had HIV-related PN while a further 1.8 % had TB-related PN. Patients with PN did not have a significantly higher risk of mortality compared to those without PN (hazard ratio (HR) 1.17 95 % CI 0.92-1.49). Patients with TB-related PN were less likely to be LTFU by 12 months (HR 0.65 95 % CI 0.44-0.97) compared to those without PN. Patients with HIV-related PN were at increased risk of persistent PN at 3 months post-ART initiation. Patients with HIV-related PN had a similar risk of recurrent PN compared to those with TB-related PN (HR 1.28 95 % CI 0.72-2.27). We demonstrate that patients with PN at initiation of ART present with advanced HIV disease. Completion of TB treatment may reduce the risk of persistent PN in patients with TB-related PN. Use of HIV drugs, even neurotoxic ones, may overall limit neuropathy.
Journal of NeuroVirology 04/2012; 18(3):162-71. · 2.85 Impact Factor
[show abstract][hide abstract] ABSTRACT: Pregnancy is a common indication for initiation of highly active antiretroviral therapy (HAART) in sub-Saharan Africa. Our objective was to evaluate how pregnancy at treatment initiation predicts virologic response to HAART.
We evaluated an open cohort of 9173 patients who initiated HAART between April 2004 and September 2009 in the Themba Lethu Clinic in Johannesburg, South Africa. Risk ratios were estimated using log-binomial regression; hazard ratios were estimated using Cox proportional hazards models; time ratios were estimated using accelerated failure time models. We controlled for calendar date, age, ethnicity, employment status, history of smoking, tuberculosis, WHO stage, weight, body mass index, hemoglobin, CD4 count and CD4 percent, and whether clinical care was free. Extensive sensitivity and secondary analyses were performed.
During follow-up, 822 nonpregnant women and 70 pregnant women experienced virologic failure. In adjusted analyses, pregnancy at baseline was associated with reduced risk of virologic failure by 6 months [risk ratio 0.66, 95% confidence limits (CL): 0.35 to 1.22] and with reduced hazard of virologic failure over follow-up (hazard ratio: 0.69, 95% CL: 0.50 to 0.95). The adjusted time ratio for failure was 1.44 (95% CL: 1.13 to 1.84), indicating 44% longer time to event among women pregnant at baseline. Sensitivity analyses generally confirmed main findings.
Pregnancy at HAART initiation is not associated with increased risk of virologic failure at 6 months or during longer follow-up.
[show abstract][hide abstract] ABSTRACT: Hepatitis B virus (HBV) infection with undetectable hepatitis B surface antigen (HBsAg) has been reported in HIV patients, but the clinical significance is unknown. This study presents the prevalence of HBV DNA in HIV-positive patients negative for all HBV serological markers and a retrospective evaluation of the clinical course of mono- and co-infection.
Of 502 HIV-positive patients, 222 tested negative for HBsAg, antibody to hepatitis B surface antigen (anti-HBs), and antibody to hepatitis B core antigen (anti-HBc). An in-house real-time PCR targeting the HBV S-region was used to quantify HBV DNA. HBV isolates were genotyped. Baseline demographic and clinical characteristics of HBV DNA-positive and HBV DNA-negative patients were described. Treatment outcomes of patients at 6, 12, and 24 months after initiation of antiretroviral therapy (ART) were summarized.
HBV DNA was detected in 5.4% (12/222) of serologically negative patients. Mean HBV viral load was 5359.2 IU/ml (standard deviation (SD) ±12 768.27). Eleven HBV isolates belonged to genotype A and one to genotype C. There were no significant differences in baseline characteristics or clinical course between the HBV DNA-positive and HBV DNA-negative groups.
We found 5.4% of the HBV serologically-negative HIV-positive patients had low levels of HBV DNA. There were no significant differences in clinical outcome between the mono- and co-infected groups.
International journal of infectious diseases: IJID: official publication of the International Society for Infectious Diseases 02/2012; 16(4):e268-72. · 2.17 Impact Factor
[show abstract][hide abstract] ABSTRACT: There are approximately 33 million individuals with HIV infection worldwide. The majority of infections are in southern Africa where hepatitis B is also known to be endemic. As access to life-saving antiretroviral therapy (ART) increases, the possibility for hepatitis B treatment resistance increases because most ART regimens contain lamivudine. Patients coinfected with HBV are therefore receiving monotherapy for HBV infection, leading to possible HBV-resistant mutants and the concurrent public health effect thereof. Additional information is needed on the prevalence of HIV-HBV coinfection and treatment response to ART. We present a summary of the information available from South Africa to date.